Ketorolac Ophthalmic Solution with Carboxymethyl Cellulose
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Solution Overview
Problem
Topical nonsteroidal anti-inflammatory drugs (NSAIDs) used in ophthalmic treatments often cause surface toxicity, keratitis, corneal subepithelial infiltrates, ulceration, and ocular irritation, such as burning or stinging, due to their concentration and preservative components, limiting bioavailability and patient comfort.
Innovation Solution
An aqueous ophthalmic formulation of ketorolac tromethamine with an optimized concentration of 0.45% and sodium carboxymethyl cellulose, within a pH range of 6.8 to 7.4, which enhances absorption and reduces adverse events without the need for preservatives, surfactants, or chelating agents, allowing for increased bioavailability and comfort.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If topical NSAIDs are used at conventional concentrations, then analgesic and anti-inflammatory activity is achieved, but ocular surface toxicity and irritation occur
Solution Approach 1:
The patent changes the concentration parameter of ketorolac tromethamine from conventional 0.5% to an optimized range of 0.4-0.45%, and adjusts the pH parameter to 6.8-7.4 (physiological pH). These parameter changes reduce ocular surface toxicity and irritation while maintaining reliable analgesic and anti-inflammatory activity, resolving the contradiction between therapeutic efficacy and harmful effects.
Solution Approach 2:
The patent introduces carboxymethyl cellulose as an intermediary substance that enhances the bioavailability and tolerability of ketorolac tromethamine. This intermediary improves drug absorption and retention on the ocular surface, allowing effective therapy at lower concentrations, thereby reducing toxicity while maintaining therapeutic reliability.
2Reliability
If higher concentration of ketorolac is used, then analgesic efficacy is improved, but burning and stinging on instillation increases
Solution Approach 1:
The patent optimizes the concentration parameter to 0.4-0.45% (lower than conventional 0.5%) and adjusts pH to physiological range (6.8-7.4). This parameter optimization maintains adequate analgesic efficacy while significantly reducing burning and stinging sensations on instillation, resolving the contradiction between efficacy and patient comfort.
Solution Approach 2:
Carboxymethyl cellulose acts as an intermediary that improves drug delivery efficiency, allowing lower ketorolac concentrations to achieve sufficient analgesic efficacy. This intermediary reduces the direct irritant effect of the drug on the ocular surface, minimizing burning and stinging while maintaining therapeutic effectiveness.
3Reliability
If conventional ketorolac formulations are used, then pain control is achieved, but bioavailability and retention time are limited
Solution Approach 1:
The patent introduces carboxnymethyl cellulose as an intermediary that significantly enhances bioavailability (greater than 200% relative to conventional formulations) and extends retention time on the ocular surface. This intermediary improves drug absorption and maintains therapeutic levels for longer periods, resolving the contradiction between adequate pain control and limited drug availability.
Solution Approach 2:
The patent adjusts the pH parameter to physiological range (6.8-7.4) and optimizes concentration to 0.4-0.45%, which improves drug stability and absorption characteristics. These parameter changes enhance bioavailability and retention time, ensuring sustained pain control without requiring frequent dosing.
4Stability of the object's composition
If preservatives and surfactants are included in the formulation, then product stability is improved, but ocular irritation and toxicity increase
Solution Approach 1:
The patent extracts and removes harmful preservatives (such as benzalkonium chloride) and surfactants from the formulation. By eliminating these harmful substances, the patent reduces ocular irritation and toxicity while maintaining product stability through optimized pH (6.8-7.4) and the use of carboxymethyl cellulose as a safe stabilizing agent.
Solution Approach 2:
The patent changes the formulation approach by adjusting pH to physiological range (6.8-7.4) and using carboxnymethyl cellulose as a stabilizing agent instead of conventional preservatives. This parameter change maintains product stability without the harmful effects of traditional preservatives and surfactants, resolving the contradiction between stability and irritation.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The formulation achieves greater than 200% relative bioavailability of ketorolac in the aqueous humor and nearly 300% in the iris-ciliary body, reducing dosing frequency and adverse events while maintaining clinical efficacy and improving patient comfort.
Implementation Method 1
the concentration of carboxnymethyl cellulose and, preferably, the pH, is selected to provide an increased absorption of ketorolac in the eye of a patient
Data Source
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AI summary
The present invention provides an aqueous ophthalmic solution comprising an effective amount of ketorolac which comprises carboxymethyl cellulose in an aqueous solution which provides increased visual acuity in users and wherein said concentration of carboxymethyl cellulose is selected to provide an increased absorption of ketorolac in the eye of a patient which is at least 130% greater than the absorption of a comparative aqueous ketorolac ophthalmic solution having the same concentration of ketorolac.